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PAX8 is the most commonly used immunomarker to link a carcinoma to the gynecologic tract; however, it lacks specificity. Through mining The Cancer Genome Atlas mRNA expression profile data, we identified SOX17 as a potential specific marker at the mRNA level for gynecologic tumors. To evaluate the utility of this marker in the identification of the gynecologic origin of a given carcinoma, we performed immunochemical staining in a large cohort of ovarian and endometrial cancer cases (n = 416), together with a large cohort of solid tumors from other organs (n = 1544) in tissue microarrays. Similar to PAX8, SOX17 was highly expressed in different subtypes of ovarian carcinoma (97.5% for SOX17 vs 97% for PAX8 in serous carcinoma, 90% vs 90% in endometrioid carcinoma, and 100% vs 100% in clear cell carcinoma), except for mucinous carcinoma (0% vs 27%), and was also highly expressed in different subtypes of endometrial carcinoma (88% vs 84% in endometrioid carcinoma, 100% vs 100% in serous and clear cell carcinoma). SOX17 was not expressed in thyroid and renal cell carcinomas, whereas PAX8 expression was high (86% and 85%, respectively). In addition, SOX17 was expressed at low levels in cervical adenocarcinoma (20%) and had no expression in cervical squamous carcinoma, mesothelioma, and carcinomas from the breast, lung, pancreas, colon, stomach, liver, bladder, and salivary gland. Our data indicate that SOX17 is not only a sensitive but also a specific marker for the origin of ovarian and endometrial carcinomas., (Copyright © 2022 United States & Canadian Academy of Pathology. Published by Elsevier Inc. All rights reserved.)

Objective: The role of sentinel lymph node (SLN) biopsy alone for staging of early-stage cervical cancer remains controversial. We aimed to determine the validity of this technique in women with early-stage cervical cancer., Methods: We retrospectively reviewed women with early-stage cervical cancer who underwent SLN mapping followed by complete pelvic lymphadenectomy as part of initial surgical management from August 1997 through October 2015. All modes of surgical approach were included. Lymphatic mapping was performed using blue dye, technetium-99m sulfur colloid (Tc-99), and/or indocyanine green (ICG). We determined SLN detection rates, sensitivity and negative predictive value., Results: One hundred eighty-eight patients were included, and 35 (19%) had lymph node metastases. At least one SLN was identified in 170 patients (90%), and bilateral SLNs were identified in 117 patients (62%). The majority of SLNs (83%) were found in the pelvis. There was no difference in detection rates between mapping agents, surgical approach, patients with and without prior conization or between patients with tumors <2cm and ≥2cm. The detection rate for bilateral SLNs was significantly lower in women with body mass index (BMI)>30kg/m 2 than in women with lower BMI (p=0.03). Metastatic disease in sentinel nodes was detected by H&E staining in 78% of cases and required ultrastaging/immunohistochemistry in 22% of cases. Only one patient had a false-negative result, yielding a sensitivity of 96.4% (95% CI 79.8%-99.8%) and negative predictive value of 99.3% (95% CI 95.6%-100%). The false-negative rate was 3.6%., Conclusions: In these women with early-stage cervical cancer, SLN biopsy had very high sensitivity and negative predictive value. We believe it is time to change the standard of care for women with early-stage cervical cancer to SLN biopsy only., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Gastric-type mucinous adenocarcinoma, an uncommon subtype of cervical carcinoma, is characterized by a distinct morphology and immunophenotype. Herein, we report a case of a 71-year-old woman who received neoadjuvant radiotherapy and chemotherapy after cervical biopsy revealed moderately differentiated invasive endocervical adenocarcinoma. Subsequently, the outside patient underwent radical hysterectomy with bilateral salpingo-oophorectomy. The post-neoadjuvant therapy hysterectomy specimen showed tumor cells with clear cytoplasm, hyperchromatic nuclei with irregular contours, which mimicked clear cell carcinoma. However, immunohistochemical staining showed that these tumor cells were positive for carcinoembryonic antigen, cytokeratin 7 (diffuse), and cytokeratin 20 (patchy), After review of the pretreatment cervical biopsy specimen, the tumor was favored to represent a gastric-type mucinous adenocarcinoma of the cervix. Pathologists should be aware of this rare tumor and its post-neoadjuvant therapy morphologic changes, which can make diagnosis more challenging.

Objectives: Lymphatic mapping studies in women with cervical cancer typically identify sentinel nodes (SLNs) in the pelvis and not the parametrium. We added India ink as a mapping agent to determine whether this would allow us to pathologically identify sentinel parametrial nodes and to test our hypothesis that the parametrial nodes are the true SLNs in women with cervical cancer., Methods: We performed lymphatic mapping and SLN biopsy in 20 women with early-stage cervical cancer undergoing radical hysterectomy or trachelectomy using a "triple injection" technique with blue dye, radiocolloid, and India ink. Pathologic processing of parametrium and nodal tissue was then performed to identify India ink in specimens., Results: On pathology review, 15 (75%) patients had a parametrial node identified, and 9 patients (45%) had bilateral parametrial nodes identified; the median number of parametrial nodes identified was 2 (range, 0-7). India ink was seen in at least 1 parametrial node in 13 (87%) of the 15 patients with a parametrial node identified pathologically. Of the 9 patients with bilateral parametrial nodes identified pathologically, only 5 (54%) had bilateral parametrial nodes containing India ink. India ink was found in 26 (44%) of 59 SLNs and only 1 (0.3%) of 289 non-SLNs. In 5 patients, India ink was seen in a SLN on the same side of the pelvis where a parametrial node was identified but not microscopically black., Conclusions: There appears to be direct drainage of cervical lesions to pelvic nodal basins bypassing small parametrial nodes. Parametrial nodes, therefore, may not always be the SLNs in women with cervical cancer., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objective: To review our experience with conization with intraoperative frozen section analysis and to compare results from our tertiary cancer center with those from 2 community hospitals., Methods: The records of all women who underwent conization with intraoperative frozen section analysis from January 1, 1997, through April 30, 2011, at The University of Texas MD Anderson Cancer Center and 2 community hospitals-The Woman's Hospital of Texas and St. Luke's Episcopal Hospital-were reviewed. Findings on pathologic analysis of frozen sections, permanent loop electrosurgical excisional procedure/conization specimens, and hysterectomy specimens were compared for each patient, and the results from the cancer center were compared to those from the community hospitals., Results: One hundred fifty-three patients met the inclusion criteria. Rates of accuracy of conization with frozen section analysis in predicting definitive pathologic findings were as follows: cervix with no residual disease after prior extirpative procedure, 96.5% (95% CI 86.9-100%); cervical squamous carcinoma in situ, 95.4% (95% CI 84.5-100%); cervical adenocarcinoma in situ, 98.7% (95% CI 92.7-100%); microinvasive carcinoma, 97.4% (95% CI 90.1-100%); and invasive carcinoma≥3 mm, 100%. Most importantly, conization with frozen section analysis was 100% accurate for triaging patients to simple or radical hysterectomy. Finally, this approach performed equally well in the cancer center with subspecialized pathologists and the 2 community hospitals with general pathologists., Conclusion: Conization with frozen section analysis is an effective technique for intraoperative triage of patients to immediate simple or radical hysterectomy and can be accurately performed in both academic and community hospitals., (Copyright © 2012 Elsevier Inc. All rights reserved.)

The findings of positron emission tomography combined with computed tomography (PET/CT) in a patient with FIGO stage IIA adenoma malignum of the uterine cervix are described in this article. PET/CT showed that the cervical tumor was intensely hypermetabolic with no evidence of disease spread. However, lymphadenectomy revealed metastatic spread to paraaortic lymph nodes. PET/CT may be useful in identifying primary site of disease in patients with adenoma malignum; however, the utility in detecting metastatic nodal disease remains to be determined.

Background: Failure to detect metastasis to para-aortic nodes in patients with locally advanced cervical cancer leads to suboptimal treatment. No previous studies have prospectively compared positron emission tomography (PET)/computed tomography (CT) with laparoscopic extraperitoneal staging in the evaluation of para-aortic lymph nodes., Methods: Sixty-five patients were enrolled; 60 were available for analysis. Patients with stage IB2-IVA cervical cancer without evidence of para-aortic lymphadenopathy on preoperative CT or magnetic resonance imaging (MRI) were prospectively enrolled. All patients underwent preoperative PET/CT. Laparoscopic extraperitoneal lymphadenectomy was performed from the common iliac vessels to the left renal vein., Results: The median age at diagnosis was 48 years (range, 23-84). The median operative time was 140 minutes (range, 89-252). The median blood loss was 22.5 mL (range, 5-150). The median length of hospital stay was 1 day (range, 0-4). The median number of lymph nodes retrieved was 11 (range, 1-39). Fourteen (23%) patients had histopathologically positive para-aortic nodes. Of the 26 patients with negative pelvic and para-aortic nodes on PET/CT, 3 (12%) had histopathologically positive para-aortic nodes. Of the 27 patients with positive pelvic but negative para-aortic nodes on PET/CT, 6 (22%) had histopathologically positive para-aortic nodes. The sensitivity and specificity of PET/CT in detecting positive para-aortic nodes when nodes were negative on CT or MRI were 36% and 96%, respectively. Eleven (18.3%) patients had a treatment modification based on surgical findings., Conclusions: Laparoscopic extraperitoneal para-aortic lymphadenectomy is safe and feasible. Surgical staging of patients with locally advanced cervical cancer should be considered before planned radiation and chemotherapy., (Copyright © 2010 American Cancer Society.)

Objective: Patients with micrometastasis to para-aortic lymph nodes may benefit from extended field chemoradiation. To determine the rate of para-aortic node micrometastasis in patients with locally advanced cervical cancer undergoing laparoscopic extraperitoneal para-aortic lymphadenectomy., Methods: We prospectively identified consecutive patients diagnosed with stage IB2-IVA biopsy-proven cervical cancer. Eligible patients included those who were candidates for treatment with radiotherapy and concurrent chemotherapy and had no evidence of para-aortic lymphadenopathy (all lymph nodes< 2 cm in diameter) by preoperative computed tomography or magnetic resonance imaging. All patients underwent preoperative positron emission tomography/computed tomography and laparoscopic extraperitoneal para-aortic lymphadenectomy. All lymph nodes were assessed for metastasis by routine hematoxylin-eosin (H&E) staining. Ultrastaging (serial sectioning) and immunohistochemical analysis were performed in H&E-negative specimens., Results: Thirteen (22%) of 60 consecutive patients had para-aortic lymph node metastases detected on routine H&E staining. Of the remaining 47 patients, one (2.1%) had evidence of micrometastasis, which was detected by ultrastaging. This patient completed whole pelvic radiotherapy and chemotherapy but had a recurrence 27 months after completion of therapy., Conclusions: The rate of para-aortic node micrometastasis in patients with locally advanced cervical cancer is low. The role of routine ultrastaging and immunohistochemical analysis in such patients remains uncertain. Future studies are needed to determine the clinical impact of para-aortic node micrometastasis in patients with locally advanced cervical cancer., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Thyroid transcription factor-1 (TTF-1) is widely used in the diagnosis of lung and thyroid carcinomas. Although there have been reports of TTF-1 immunoreactivity in tumors other than those originating in the lung or thyroid, endocervical and endometrial adenocarcinomas have not been studied in large numbers. Our study provides data regarding the incidence and distribution of TTF-1 expression in these tumors. Twenty-eight endocervical (9 well, 12 moderately, and 7 poorly differentiated), 32 endometrioid endometrial adenocarcinomas (11 grade I, 8 grade II, and 13 grade III), and 13 uterine serous carcinomas were retrieved and stained with TTF-1. None of the tumors had a neuroendocrine component. The hematoxylin and eosin and anti-TTF-1 antibody stained sections were reviewed, and the presence and distribution of TTF-1 nuclear positivity was recorded. A semiquantitative grading system used to evaluate the distribution of TTF-1 staining (0 = negative, 1+ = <5%, 2+ = 5% to 25%, 3+ = 26% to 50%, 4+ = 51% to 75%, and 5+ = >75%). TTF-1 expression was seen in 1 of 28 (4%) of the endocervical adenocarcinomas and this was 4+ in distribution. The positive endocervical carcinoma was poorly differentiated. TTF-1 expression was present in 6 of 32 (19%) of the endometrioid adenocarcinomas (1 grade I, 2 grade II, and 3 grade III) and varied from 1+ to 4+ in distribution. Only 2 of 32 (6%) of the endometrioid adenocarcinomas stained diffusely (4+). There was no apparent correlation between the degree of differentiation and TTF-1 positivity in the adenocarcinomas. Three of 13 (23%) serous carcinomas were also positive (1 case 5+ and 2 cases 1+). Although TTF-1 is generally considered to be a relatively specific marker for lung and thyroid neoplasms, the occasional expression of endometrial and endocervical carcinomas should be kept in mind when evaluating neoplasms of uncertain origin. It should also be taken into consideration in the evaluation of adenocarcinomas involving the lung in patients with a history of a gynecologic malignancy.